Primary infection with varicella zoster virus (VZV) causes chicken pox, usually in children and young adults. Chicken pox is a highly contagious disease characterized by a vesicular skin rash that can be severe, most commonly in adult males, or associated with serious complications in pregnant women and immunocompromised individuals. A live attenuated varicella virus vaccine (VARIVAX™, Merck, Whitehouse Station, N.J.) prepared from the Oka/Merck attenuated strain of varicella is available for the prevention of chicken pox in individuals 12 months of age and older. The viral strain in VARIVAX™ was initially isolated from a child infected with varicella and attenuated through serial passage in embryonic guinea pig cell cultures, followed by propagation in human diploid cell cultures (WI-38 and MRC-5). VARIVAX™ induces both humoral and cell-mediated immunity in vaccinated individuals.
Although clinical manifestations of chicken pox typically resolve without medical intervention within a short period of time, the VZV can remain latent in sensory neurons for many years following infection. Reactivation and replication of latent VZV, often decades later, can lead to herpes zoster (HZ), commonly known as shingles, a unilateral, painful rash that is generally limited to a single dermatome. Such VZV reactivation correlates with a decline in cell-mediated immunity, which occurs in the elderly or those who are immunocompromised (Weinberg et al., Journal of Infectious Diseases (2009) 200: 1068-77; Oxman et al., New England Journal of Medicine 22: 2271-84 (2005)). In some patients, pain associated with HZ can persist for months or even years after the HZ rash has healed, a complication referred to as post-herpetic neuralgia (PHN). Opthalmic zoster may also be associated with HZ, as well as other neurological complications.
A live attenuated vaccine (ZOSTAVAX®, Merck, Whitehouse Station, N.J.) is currently available for the prevention of herpes zoster in healthy individuals aged 50 or over (U.S. Pat. Nos. 6,214,354 and 5,997,880; G. M. Keating, Drugs DOI 10.1007/s40265-013-0088-1 (2013)). This vaccine has markedly reduced the adverse impacts of HZ in immunocompetent patient populations by boosting cell-mediated immunity to VZV (Oxman, M N, Clin. Infect. Dis. (2010) 51(2):197-213; Sanford and Keating, Drugs Aging (2010) 27(2):159-76; Oxman et al., N Engl. J. Med. (2005) 352: 2271-83). Results of the Shingles Prevention Study (SPS) indicate that in individuals≥60 years of age, ZOSTAVAX™ reduced the incidence of HZ by 51%, as well as HZ-associated pain, including PHN in immunocompetent adults 60 years of age or older (Oxman et al. 2005, supra). In adults 50-59 years of age, ZOSTAVAX™ reduced the incidence of HZ by 69.8%. Further reductions in the rate of HZ, particularly in the advanced elderly, are needed.
Despite the successful reduction of burden of illness associated with VZV by live attenuated vaccines, there remains an interest in development of additional VZV vaccines for different patient populations or different methods of administration, which may increase the immune response against VZV. The boost in vaccine-induced CMI varies with age of the recipient and may gradually decline over time (M. J. Levin, Current Opinion in Immunology 24: 494-500 (2012)). Thus, new methods of immunization, such as addition of further vaccine doses to the treatment regimen and/or use of higher dosages are being tested to increase CMI and/or duration of protection (Levin, supra).